A linear ontogeny accounts for the development of naive, memory and tumour-infiltrating regulatory T cells in mice.

Foxp3 + Regulatory T cells (Treg) are a subset of CD4 + T cells that play critical functions in maintaining tolerance to self antigens and suppressing autoimmunity, regulating immune responses to pathogens and have a role in the pathophysiology of anti-tumoural immunity. Treg ontogeny is complex since they are generated following recognition of self antigens in the thymus during normal T cell development (thymic Treg), but are also induced from mature conventional T cells when activated by foreign antigen with appropriate additional cues (inducible Treg). How these distinct ontogenic pathways contribute to the maintenance and function of the mature Treg compartment in health and disease remains unclear. Here, we use a combination of fate mapping approaches in mice to map the ontogeny of Treg subsets throughout life and estimate rates of production, loss and self-renewal. We find that naive and effector/memory (EM) Treg subsets exhibit distinct dynamics but are both continuously replenished by de novo generation throughout life. Using an inducible Foxp3-dependent Cre fate reporter system, we show that naive Treg and not conventional T cells, are the predominant precursors of EM Treg in adults. Tonic development of new EM Treg is not influenced by foreign antigens from commensals, rather suggesting a role for self recognition. To investigate the ontogeny of Treg development in malignant disease, we used the same fate reporter systems to characterise the Treg infiltrate of three different model tumours. In all three cases, we found that Treg derived from pre-existing, EM Treg. Together, these results reveal a predominantly linear pathway of Treg development from thymic origin to EM Treg associated with pathophysiology of malignant disease, that is driven by self antigen recognition throughout.

Time-gated luminescent probes for lysosomal singlet oxygen: Synthesis, characterizations and bioimaging applications.

BACKGROUD: Single oxygen (1O2), the molecular oxygen at its excited state, plays a crucial role in the photodynamic therapy (PDT) of some diseases owing to its strong oxidizing property to destroy malignant cells. Although the fluorescent probe technique has proven its powerful application abilities for detection of 1O2 in biological systems, most of the reported fluorescent probes suffered from the interference of background autofluorescence of biological samples. It is clear that the real-time and in situ, background-free fluorescent detection of 1O2 generated in live cells, especially in some organelles, is of great significance for understanding the action mechanism of PDT drugs. RESULTS: By introducing a lysosome-anchoring motif, a morpholine moiety, into a 1O2-specifically-reactive terpyridine polyacid ligand, [4'-(9-anthryl)-2,2':6',2″-terpyridine-6,6″-diyl] bis(methylenenitrilo) tetrakis (acetic acid) (ATTA), and chelating with lanthanide ions (Eu3+ or Tb3+), two lanthanide complex-based "turn-on" luminescent probes that can be used for the background-free time-gated luminescent (TGL) detection of lysosomal 1O2, Lyso-ATTA-Eu3+ and Lyso-ATTA-Tb3+, have been developed. The probes exhibit fast luminescence responses (within 2.5 min) towards 1O2 with high selectivity and sensitivity (<0.75 µM) in a wide pH range (4-11). And the excellent lysosome-localization performance of the probes allowed them to be used for the monitoring of endogenous 1O2 in lysosomes, which enabled the variability of lysosomal-1O2 concentrations induced by different photosensitizers to be successfully discriminated. Furthermore, by doping Lyso-ATTA-Eu3+ into the polyethylene glycol (PEG) hydrogel, the smart luminescent sensor film, PEG-Lyso-ATTA-Eu3+, was prepared, and successfully used for the detection of the on-site 1O2 production during the PDT process of psoriatic disease in model mice. SIGNIFICANT: Two lysosome-targetable background-free TGL probes for 1O2 were firstly reported. The developed smart luminescent sensor film could be a powerful tool for the clinical monitoring of PDT on skin diseases without using sophisticated and expensive instruments.

Effect of various types of photodynamic therapy on inflammatory and non-inflammatory lesions in patients with acne: A network meta-analysis of randomized controlled trials.

BACKGROUND: Recent studies have demonstrated that photodynamic therapy (PDT) is safe and effective in treating acne vulgaris. The present study aimed to evaluate various PDTs on inflammatory and non-inflammatory lesions in patients with acne by a network meta-analysis (NMA) of randomized controlled trials (RCTs). METHODS: The researchers of this paper searched PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases from inception to March 2022 to identify suitable RCTs. The included studies were evaluated for methodological quality using the Cochrane bias risk assessment tool. Twenty-one RCTs were included, with a total sample size of 898 participants. RESULTS: Network meta-analysis (NMA) revealed that indocyanine green (ICG) + near-infrared (NIR) diode laser, ICG+830 nm light-emitting diode (LED), indole-3-acetic acid (IAA) + 520 nm LED, and 5-aminolevulinic acid (ALA) + sunlight demonstrated obvious curative effects in patients with acne vulgaris. Importantly, ICG+NIR diode laser provided the greatest improvement in both inflammatory and non-inflammatory acne lesions (surface under the cumulative ranking curve [SUCRA]: 84.4% and 93.5%, respectively). CONCLUSIONS: Based on the NWM and SUCRA ranking, ICG + NIR diode laser can be considered more effective in treating acne than the other PDTs of the RCTs. However, this conclusion should be interpreted with caution due to the limitations of the present study.

Mitochondria-Targetable Ratiometric Time-Gated Luminescence Probe Activated by Selenocysteine for the Visual Monitoring of Liver Injuries.

Liver injury can result from various risk factors including diabetes, virus, alcohol, drugs, and other toxins, which is mainly responsible for global mortality and morbidity. Selenocysteine (Sec), as the main undertaker of selenium function in the life system, features prominently in a series of hepatic injuries and has close association with the pathological progression of liver injuries. Here, we report a mitochondria-targetable lanthanide complex-based probe, Mito-NPTTA-Tb3+/Eu3+, that can be used for accurately determining Sec in live cells and laboratory animals via the ratiometric time-gated luminescence (TGL) technique. This probe is composed of 2,2':6',2″-terpyridine-Tb3+/Eu3+ mixed complexes as the luminophore, 2,4-dinitrophenyl (DNP) as the responsive moiety and a lipophilic triphenylphosphonium cation (PPh3+) as the mitochondria-targeting moiety. Upon reaction with Sec, accompanied by the cleavage of DNP from the probe molecule, the I540/I690 ratio of the probe increased by 55 times, which enabled Sec to be detected with the ratiometric TGL method. After being incubated with living cells, the probe molecules were selectively accumulated in mitochondria to allow the mitochondrial Sec to be successfully imaged under the ratiometric TGL mode. Importantly, using this probe coupled with the ratiometric TGL imaging technique, the fluctuations of liver Sec in various liver injuries of model mice induced by diabetes, drug, toxin, and alcohol were precisely monitored, revealing that Sec plays an important antioxidant role during the oxidative stress process in liver injury, and the Sec levels have a close interrelationship with the degree of liver injury. All the results suggest that the new probe Mito-NPTTA-Tb3+/Eu3+ could be a potential tool for the accurate diagnosis of liver injury.

Qualitative and quantitative analysis of the influence of biodiesel fatty acid methyl esters on iodine value.

Iodine value (IV) is an indicator to evaluate the degree of unsaturation (DU) of biodiesel. It reflects the biodiesel degradation and oxidation stability (OS) and also has an effect on viscosity, low-temperature flow properties (LTFP), and the combustion performance. To construct a theoretical system for the simultaneous optimization of LTFP and OS of biodiesel using IV, 52 measured experimental data are used to investigate the qualitative and quantitative relationship between IV and biodiesel composition. The relationships between biodiesel physicochemical properties and IV are investigated in this work. The qualitative analysis shows that the poly-unsaturated fatty acid methyl esters (FAMEs) contribute to an increase in IV, whereas saturated and mono-unsaturated FAMEs decrease IV. Multiple linear regression (MLR) and artificial neural network (ANN) are used to estimate IV from FAMEs. The correlation coefficient, root mean squared error (RMSE), and mean absolute percentage error (MAPE) are respectively 0.976, 2.45, and 1.76% for the MLR model and 0.983, 2.14, and 1.57% for the back propagation neural network (BPNN) model; these values indicate the high accuracy of these methods. The performances of the proposed models were compared with three existing IV prediction models and validated by another databank. The results indicate that the application of the developed BPNN model is better and more comprehensive. Additionally, a preliminary conclusion is that biodiesel with a low percentage of both long-chain saturated and poly-unsaturated FAMEs can have solidifying point (SP) and OS in the proper range. Biodiesel with a low IV is generally more combustible and efficient.

Strengthening practical continuous-variable quantum key distribution against measurement angular error.

The optical phase shifter that constantly rotates the local oscillator phase is a necessity in continuous-variable quantum key distribution systems with heterodyne detection. In previous experimental implementations, the optical phase shifter is generally regarded as an ideal passive optical device that perfectly rotates the phase of the electromagnetic wave of 90∘. However, the optical phase shifter in practice introduces imperfections, mainly the measurement angular error, which inevitably deteriorates the security of the practical systems. Here, we will give a concrete interpretation of measurement angular error in practical systems and the corresponding entanglement-based description. Subsequently, from the parameter estimation, we deduce the overestimated excess noise and the underestimated transmittance, which lead to a reduction in the final secret key rate. Simultaneously, we propose an estimation method of the measurement angular error. Next, the practical security analysis is provided in detail, and the effect of the measurement angular error and its corresponding compensation scheme are demonstrated. We conclude that measurement angular error severely degrades the security, but the proposed calibration and compensation method can significantly help improve the performance of the practical CV-QKD systems.

A visible-light-excitable mitochondria-targeted europium complex probe for hypochlorous acid and its application to time-gated luminescence bioimaging.

Development of fluorescent/luminescent probes for rapid, selective and sensitive detection of reactive oxygen species (ROS) is of great significance for understanding the roles of ROS in pathophysiological processes. In the present research, a visible-light-excitable Eu3+ complex-based probe, Eu(L)3(DPBT), is designed and synthesized for the time-gated luminescence (TGL) determination of hypochlorous acid (HClO) in vitro and in vivo. The proposed probe exhibits a rapid, selective and sensitive TGL response to HClO, and excellent localization of mitochondria in living cells with low cytotoxicity. These features allow the probe to be used for the TGL sensing and imaging of HClO formation in mimic inflammatory cells at a subcellular level, as well as in endotoxin-induced liver injury and rheumatoid arthritis in live mice. In addition, by immobilizing the probe in the PEG hydrogel, the smart sensor films with rapid response to HClO were prepared, and successfully used for the real-time monitoring of HClO generation in mouse wounds, in order to distinguish the infected wounds from acute ones. Overall, this study provides a useful tool for the clinical monitoring and treatment of wound diseases.

Bioferroelectric Properties of Glycine Crystals.

Biological ferroelectric materials have great potential in biosensing and disease diagnosis and treatment. Glycine crystals form the simplest bioferroelectric materials, and here we investigate the polarizations of its ß- and γ-phases. Using density functional theory, we predict that glycine crystals can develop polarizations  even larger than those of conventional inorganic ferroelectrics. Further, using systematic molecular dynamics simulations utilizing polarized crystal charges, we predict the Curie temperature of γ-glycine to be 630 K, with a required coercive field to switch its polarization states of 1 V·nm-1, consistent with experimental evidence. This work sheds light on the microscopic mechanism of electric dipole ordering in biomaterials, helping in the material design of novel bioferroelectrics.